8-(3-methylsulfanyl-phenyl)-[1,7]naphthyridin-6-ylamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 8-(3-methylsulfanyl-phenyl)-[1,7]naphthyridin-6-ylamine
• 英文别名: 8-(3-methylsulfanylphenyl)-1,7-naphthyridin-6-amine
• 化学式: C₁₅H₁₃N₃S
• 分子量: 267.354
• InChiKey: FIGLLAFQZFIVHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-(3-methylsulfanyl-phenyl)-[1,7]naphthyridin-6-ylamine 在 三甲基氯硅烷 、 1,2-二溴乙烷 、 锌 、 sodium nitrite 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 4-[8-(3-Methylsulfanyl-phenyl)-[1,7]naphthyridin-6-yl]-cyclohexanecarboxylic acid ethyl ester
  参考文献：
  名称：

  Solubility-Driven Optimization of Phosphodiesterase-4 Inhibitors Leading to a Clinical Candidate

  摘要：

  The solubility-driven optimization of a series of 1,7-napthyridine phosphodiesterase-4 inhibitors is described. Directed structural changes resulted in increased aqueous solubility, enabling superior pharmacokinetic properties with retention of PDE4 inhibition. A range of potent and orally bioavailable compounds with good in vivo efficacy in animal models of inflammation and reduced emetic potential compared to previously described drugs were synthesized. Compound 2d was taken forward as a clinical candidate for the treatment of COPD.

  DOI：

  10.1021/jm300459a
• 作为产物：
  描述：

  3-吡啶乙腈 在 氢溴酸 、 双氧水 、 溶剂黄146 、 二甲氨基甲酰氯 作用下， 以 甲苯 为溶剂， 反应 4.5h， 生成 8-(3-methylsulfanyl-phenyl)-[1,7]naphthyridin-6-ylamine
  参考文献：
  名称：

  Solubility-Driven Optimization of Phosphodiesterase-4 Inhibitors Leading to a Clinical Candidate

  摘要：

  The solubility-driven optimization of a series of 1,7-napthyridine phosphodiesterase-4 inhibitors is described. Directed structural changes resulted in increased aqueous solubility, enabling superior pharmacokinetic properties with retention of PDE4 inhibition. A range of potent and orally bioavailable compounds with good in vivo efficacy in animal models of inflammation and reduced emetic potential compared to previously described drugs were synthesized. Compound 2d was taken forward as a clinical candidate for the treatment of COPD.

  DOI：

  10.1021/jm300459a

文献信息

• [EN] [1,7]NAPHTHYRIDINES AS PDE4 INHIBITORS<br/>[FR] [1,7]NAPHTHYRIDINES UTILISES EN TANT QU'INHIBITEURS DE LA PDE4
  申请人：NOVARTIS AG

  公开号：WO2004055013A1

  公开（公告）日：2004-07-01

  Compounds of Formula (I) in free or salt form, wherein R1, R2 and R3 have the meanings as indicated in the specification, are useful for treating conditions mediated by of phosphodiesterase type 4 or the down-regulation or inhibition of TNF-α release, particularly obstructive or inflammatory airways diseases. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described.

  公式（I）的化合物以自由形式或盐形式存在，其中R1、R2和R3的含义如规范中所示，可用于治疗由磷酸二酯酶4型介导或TNF-α释放的下调或抑制引起的情况，特别是阻塞性或炎症性气道疾病。还描述了含有这些化合物的药物组合物以及制备这些化合物的过程。
• [1,7]naphthyridines as pde4 inhibitors
  申请人：Denholm Alastair

  公开号：US20060058338A1

  公开（公告）日：2006-03-16

  Compounds of formula I in free or salt form, wherein R 1 , R 2 and R 3 have the meanings as indicated in the specification, are useful for treating conditions mediated by of phosphodiesterase type 4 or the down-regulation or inhibition of TNF-α release, particularly obstructive or inflammatory airways diseases. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described.

  公式I中自由或盐形式的化合物，其中R1，R2和R3具有规范中所示的含义，可用于治疗由磷酸二酯酶4型介导的疾病或TNF-α释放的下调或抑制，特别是阻塞性或炎症性空气道疾病。还描述了包含该化合物的制药组合物和制备该化合物的过程。
• [1,7]naphthyridines as PDE4 inhibitors
  申请人：Novartis AG

  公开号：US07468370B2

  公开（公告）日：2008-12-23

  Compounds of formula I in free or salt form, wherein R1, R2 and R3 have the meanings as indicated in the specification, are useful for treating conditions mediated by of phosphodiesterase type 4 or the down-regulation or inhibition of TNF-α release, particularly obstructive or inflammatory airways diseases. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described.

  公式I的化合物，无论是自由形式还是盐形式，其中R1、R2和R3的含义如规范中所示，可用于治疗由磷酸二酯酶4型介导或TNF-α释放的下调或抑制引起的情况，特别是阻塞性或炎症性气道疾病。还描述了包含这些化合物的制药组合物和制备这些化合物的方法。
• [1,7]NAPHTHYRIDINES AS PDE4 INHIBITORS
  申请人：Novartis AG

  公开号：EP1575950A1

  公开（公告）日：2005-09-21
• US7468370B2
  申请人：——

  公开号：US7468370B2

  公开（公告）日：2008-12-23